Frequency-Dependent Variability of Pulse Wave Transit Time: Pilot Study.

The dynamics of the pulse wave (PW) associated with the PW transit time variability (PWTTV) determines the peripheral pulse rate variability, which is used as a surrogate for heart rate variability (HRV). The aim of the work is to analyze the frequency-dependent dynamics of PWTTV and to identify the possible frequency-phase modulation of PW velocity oscillations on the transit from the heart to the soft tissues of the distal parts of the upper extremities. RR-interval recordings and synchronous records of photoplethysmograms of 12 conditionally healthy subjects from the PhysioNet open database were used in this work. Using the Hilbert-Huang transform 3 spectral components of PWTTV and HRV were identified. It was shown that the amplitudes of PWTTV oscillations were many times (up to 8.4 times) smaller than the amplitudes of HRV, and the peaks of PWTTV spectral components were shifted towards higher frequencies than those of HRV. Functional relations between PWTTV and HRV, which can determine the phase modulation of periodic changes in the PW propagation velocity, were revealed.

Spectral Analysis of Heart Rate Variability Based on the Hilbert-Huang Method.

Analysis of heart rate variability (HRV) is widely used for noninvasive assessment of the state of the regulation systems of the heart. The aim of this study was to evaluate the capabilities of the Hilbert-Huang method for calculating spectral parameters of HRV in comparison with the commonly used Fourier analysis. Fourier analysis allows estimation of averaged spectral amplitudes and power of HRV oscillations in fixed frequency intervals, which are associated with the activity of sympathetic, parasympathetic, and humoral regulation systems. Using the Hilbert-Huang method, we revealed four spectral components, described by Gaussian functions, in which HRV oscillations are concentrated, and showed the absence of fixed boundaries between them. The obtained energy quantitative characteristics of the spectral components of heart rhythm oscillations can serve as the basis for diagnostic methods of heart rhythm regulation, supplementing the commonly used ones.

Localization of Mechanisms of Amplitude-Frequency Modulation of Pulse Blood Perfusion of the Soft Tissue Microvasculature. Pilot Study.

Peripheral blood flow analysis is used for noninvasive assessment of the cardiovascular system. The aim was to investigate the possibility of applying Hilbert-Huang spectral analysis (HH) to localize the mechanisms of nonlinear regulation of blood perfusion dynamics in the soft tissues of distal areas of the hands in human. In 9 healthy subjects, synchronous recording of photoplethysmograms (PPG) from the index fingers of the hands was performed. Using a band-pass filter, a cardiac signal was extracted from the PPG, which was separated into the carrier and modulating components. The latter was subjected to decomposition into empirical modes by HH method. Five modes were detected, for which the coherence between the hands was evaluated. The frequencies of the modes fell within the conventional frequency intervals of skin blood flow oscillations, and the coherence was 0.6. A decreased depth of modulation in the left hand compared to the right hand was shown. The results indicate a central origin of the nonlinear regulation of the dynamics of tissue blood perfusion in the hands.

Role of additive stochastic modulation of the heart activity in the formation of 0.1-Hz blood flow oscillations in the human cardiovascular system.

In the framework of our previous hypothesis about the participation of structural and hydrodynamic properties of the vascular bed in the formation of the 0.1-Hz component of blood flow oscillations in the human cardiovascular system and on the basis of the reduced hydrodynamic model, the role of additive stochastic perturbations of the operation of the single-chamber pump that simulates the heart was investigated. It was shown that aperiodic noise modulation of the rigidity of the walls of the pump or its valves generates low-frequency oscillations of pressure and blood flow velocity of arterial vascular bed with the maximum amplitude at a frequency close to 0.1 Hz.

[Effects of the Airway Obstruction on the Skin Microcirculation in Patients with Bronchial Asthma].

Background: Pulmonary hemodynamic disorders depend on the inflammatory phases and severity of the obstructive syndrome. However, the effect of asthma bronchial obstruction on the state of peripheral hemodynamics remains insufficiently known. Aims: To study the effects of airway obstruction on skin blood flow parameters and its regulatory systems in patients with persistent atopic bronchial asthma in the remission state. Materials and Methods: A comparative study of the skin peripheral blood flow in patients with bronchial asthma with severe airway obstruction (1st group) and without obstruction (2nd group) was conducted. 20 patients with confirmed diagnosis of atopic asthma of 50­74 years old participated in the study. All patients received basic therapy in a constant dosing of high doses of inhaled glucocorticosteroids/long-acting beta-2-agonists. The control group included 20 healthy volunteers without evidence of bronchial obstruction. The study lasted for 3 months. The forced expiratory volume in 1 s (FEV1) was used to evaluate the bronchial obstruction by spirometry technique. Skin blood perfusion changes were recorded by laser Doppler flowmetry at rest and in response to short-term local ischemia. Registered peripheral blood flow signals were examined using the amplitude temporal filtering in five frequency intervals to identify the functional features of the peripheral blood flow regulation systems. Results: Consistent two-fold decrease of the oscillation amplitudes was found in the neurogenic interval at rest (p=0.031), as well as in the myogenic (p=0.043; p=0.031) and endothelial intervals (p=0.037; p≤0.001) both at rest and during the postocclusive reactive hyperemia respectively in the 1st group of patients with bronchial obstruction (FEV1 <80%) compared with the control group. No significant changes were revealed for skin blood flow parameters in the 2nd patient group (without obstruction, FEV1 >80%) in comparison to control subjects. Conclusions: The presence of bronchial obstruction has a significant impact on the changes of the amplitudes of skin blood flow oscillations in patients with bronchial asthma in the myogenic, neurogenic and endothelial intervals.

[Physiological features of skin ageing in human].

The issue deals with the actual problem of gerontology, notably physiological features of human skin ageing. In the present review the authors have considered the kinds of ageing, central factors, affected on the ageing process (ultraviolet radiation and oxidation stress), as well as the research guidelines of the ageing changes in the skin structure and fuctions: study of mechanical properties, microcirculation, pH and skin thickness. The special attention has been payed to the methods of assessment of skin blood flow, and to results of investigations of age features of peripheral microhemodynamics. The laser Doppler flowmetry technique - one of the modern, noninvasive and extensively used methods for the assessmant of skin blood flow microcirculation system has been expanded in the review. The main results of the study of the ageing changes of skin blood perfusion using this method has been also presented.

[Changes in the chromatin structure of lymphoid cells under the influence of low-intensity extremely high-frequency electromagnetic radiation against the background of inflammatory process].

Using the alkaline single cell gel electrophoresis technique (comet assay), changes in chromatin structure of peripheral blood leukocytes and peritoneal neutrophils have been studied in mice exposed to low-intensity extremely high-frequency electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, 20 min at 1 h after induction of inflammation) against the background of the systemic inflammatory process. It was revealed that the exposure of mice with the developing inflammation leads to a pronounced decrease in the level of DNA damage to peripheral blood leukocytes and peritoneal neutrophils. It is supposed that the changes in the chromatin structure of lymphoid cells have a genoprotective character in the inflammatory process and can underlie the mechanisms of realization of antiinflammatory effects of the electromagnetic radiation.

[Responses of thymocytes and splenocytes to low-intensity extremely high-frequency electromagnetic radiation in normal mice and in mice with systemic inflammation].

Changes in T cell subsets and expression of cytokine genes in thymocytes and splenocytes after exposure of BAL/c mice to low-intensity extremely high-frequency electromagnetic radiation (42.2 GHz, 0.1 mW/cm2, exposure duration 20 min) under normal conditions and in systemic inflammation were studied using flow cytometry and the methods of reverse transcription and real-time polymerase chain reaction. It was found that the number of CD4+ and CD8+ T cells statistically significantly increased in the thymus and considerably decreased in the spleen of exposed animals. Apparently, the exposure of animals leads to an intensification of the host defense, by activating the T-cellular immunity. As for effector functions, the increased expression of IL-1beta and IFNgamma genes in thymocytes and essentially enhanced expression of IL-1beta, IL-10, and TNFalpha genes in splenocytes were observed in mice exposed against the background of a progressive inflammatory process. The experimental data obtained specify that the directed (anti-inflammatory) response of an organism to a specific combination of effective exposure parameters of electromagnetic radiation can be realized by the activation of particular immunocompetent cells and changes in the cytokine profile.

[Age features of the dynamics of the oscillation amplitudes of the peripheral skin blood flow during the postocclusive reactive hyperemia].

The study of age-related changes of peripheral microhemodynamics was performed by laser Doppler flowmetry in 60 healthy volunteers. To determine the reaction of the microvascular system in response to short-term ischemia an occlusion test was used. To study the dynamics of the oscillation amplitudes of the peripheral blood flow the time-amplitude analysis on the basis of continuous adaptive wavelet filtration was used. It was found that the amplitudes of the oscillation in the range of heart rate in each age group reached its maxima with a delay after the occlusion stopping, whereas in the range of respiratory rhythm such delay was not observed. It is assumed that the formation ofhyperemic response to short-term ischemia occurs due to the preferential effect of arterio-arteriolar level, and the dynamics of the amplitudes in the range of respiratory rhythm reflects the devastation ofvenular level after occlusion stop. The observed age-related decreases of the maximum amplitudes in the range of myogenic, neurogenic and endothelial rhythms in response to shortterm ischemia demonstrate an age reduction limits of the peripheral blood flow regulation by related systems.

[Adaptive wavelet analysis of oscillations of the cutaneous peripheral blood flow in human].

The main principles of the method for the spectral timing analysis of the peripheral blood flow oscillations, obtained by laser Doppler flowmetry, have been presented. The method allows one to investigate the oscillations in a wide frequency range both in stationary and nonstationary conditions during the performance of functional tests. The potential of the method has been demonstrated in experiments with the reaction of the microvascular bed to the transcutaneous iontophoretic introduction of an acetylcholine chloride solution. The major advantage of the method as compared to the traditional wavelet analysis is a significant increase in the "effective" length of the signal analyzed. This allows a correct analysis of the low-frequency component of much shorter LDF recordings than those used in the traditional wavelet analysis.

[Antitumor effect of low-intensity extremely high-frequency electromagnetic radiation on a model of solid Ehrlich carcinoma].

The influence of different exposure regimes of low-intensity extremely high-frequency electromagnetic radiation on the growth rate of solid Ehrlich carcinoma in mice has been studied. It was shown that, at an optimum repetition factor of exposure (20 min daily for five consecutive days after the tumor inoculation), there is a clearly pronounced frequency dependence of the antitumor effect. The analysis of experimental data indicates that the mechanisms of antitumor effects of the radiation may be related to the modification of the immune status of the organism. The results obtained show that extremely high-frequency electromagnetic radiation at a proper selection of exposure regimes can result in distinct and stable antitumor effects.

[Age-dependent characteristics of the skin peripheral blood flow oscillations by nonlinear dynamics methods in humans].

Study of peripheral microhaemodynamics was carried out with laser Doppler flowmetry in healthy volunteers of different age groups. The ageing changes in the state of the skin peripheral blood flow, in the functioning of separate links and regulatory systems ofmicrovascular bed have been estimated in terms of relative entropy and fractal dimension values. The revealed significant age-dependent decrease of relative entropy values in the respiratory rhythm ranges, the neurogenic and myogenic activities yielded some evidence concerning the reduction of the microcirculation system chaotic changes within these frequency ranges during the ageing. The significant increase of fractal dimension values in the ranges of cardio-rhythm and the endothelial activity in the oldest group with the mean age of 77 years indicated that the structural complexity of the oscillations in these frequency ranges increased during ageing.

Anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation: frequency and power dependence.

Using a model of acute zymosan-induced footpad edema in NMRI mice, the frequency and power dependence of anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR) was found. Single whole-body exposure of animals to EHF EMR at the intensity of 0.1 mW/cm(2) for 20 min at 1 h after zymosan injection reduced both the footpad edema and local hyperthermia on average by 20% at the frequencies of 42.2, 51.8, and 65 GHz. Some other frequencies from the frequency range of 37.5-70 GHz were less effective or not effective at all. At fixed frequency of 42.2 GHz and intensity of 0.1 mW/cm(2), the effect had bell-shaped dependence on exposure duration with a maximum at 20-40 min. Reduction of intensity to 0.01 mW/cm(2) resulted in a change of the effect dependence on exposure duration to a linear one. Combined action of cyclooxygenase inhibitor sodium diclofenac and EHF EMR exposure caused a partial additive effect of decrease in footpad edema. Combined action of antihistamine clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that arachidonic acid metabolites and histamine are involved in realization of anti-inflammatory effects of low-intensity EHF EMR.

[Assessment of the changes in regulatory systems of human's skin blood flow during local heating].

The mechanisms of thermal regulation of skin blood flow during local heating to 35, 40 and 45 'C have been studied by the method of laser Doppler flowmetry in healthy volunteers. To estimate the state of microvascular bed the continuous wavelet-transform spectral analysis has been used. The amplitudes of fluxmotions in the range of blood flow active modulation significantly increase during local heating to 35 degrees C. The amplitudes of blood flow oscillations in the ranges of cardiorhythm and respiratory rhythm increase during local heating to 40 degrees C. The high amplitude oscillations in the range of myogenic activity are maintained. The amplitude of oscillations in the range of endothelial activity distinctly decreases and the oscillations in the range of neurogenic activity are inhibited. Local heating to 45 degrees C results in a significant decreasing of the oscillation amplitudes in the range of myogenic activity, and the amplitudes of cardio- and respiratory spectral components amount to their peak values among the temperatures of local heating under study.

[Thermoelastic excitation of acoustic waves in biological models under the effect of the high peak-power pulsed electromagnetic radiation of extremely high frequency].

The capability of high peak-power pulsed electromagnetic radiation of extremely high frequency (35,27 GHz, pulse widths of 100 and 600 ns, peak power of 20 kW) to excite acoustic waves in model water-containing objects and muscular tissue of animals has been experimentally shown for the first time. The amplitude and duration of excited acoustic pulses are within the limits of accuracy of theoretical assessments and have a complex nonlinear dependence on the energy input of electromagnetic radiation supplied. The velocity of propagation of acoustic pulses in water-containing models and isolated muscular tissue of animals was close to the reference data. The excitation of acoustic waves in biological systems under the action of high peak-power pulsed electromagnetic radiation of extremely high frequency is the important phenomenon, which essentially contributes to the understanding of the mechanisms of biological effects of these electromagnetic fields.

[Pharmacological analysis of anti-inflammatory effects of low-intensity extremely high-frequency electromagnetic radiation].

The anti-inflammatory effect of low-intensity extremely high-frequency electromagnetic radiation (EHF EMR, 42.0 GHz, 0.1 mW/cm2) was compared with the action of the known anti-inflammatory drug sodium diclofenac and the antihistamine clemastine on acute inflammatory reaction in NMRI mice. The local inflammatory reaction was induced by intraplantar injection of zymosan into the left hind paw. Sodium diclofenac in doses of 2, 3, 5, 10, and 20 mg/kg or clemastine in doses of 0.02, 0.1, 0.2, 0.4, and 0.6 mg/kg were injected intraperitoneally 30 min after the initiation of inflammation. The animals were whole-body exposed to EHF EMR for 20 min at 1 h after the initiation of inflammation. The inflammatory reaction was assessed over 3 - 8 h after the initiation by measuring the footpad edema and hyperthermia of the inflamed paw. Sodium diclofenac in doses of 5 - 20 mg/kg reduced the exudative edema on the average by 26% as compared to the control. Hyperthermia of the inflamed paw decreased to 60% as the dose of was increased diclofenac up to 20 mg/kg. EHF EMR reduced both the footpad edema and hyperthermia by about 20%, which was comparable with the effect of a single therapeutic dose of diclofenac (3 - 5 mg/kg). The combined action of diclofenac and the exposure to the EHF EMR caused a partial additive effect. Clemastine in doses of 0.02-0.4 mg/kg it did not cause any significant effects on the exudative edema, but in a dose of 0.6 mg/kg it reduced edema by 14 - 22% by 5 - 8 h after zymosan injection. Clemastine caused a dose-dependent increase in hyperthermia of inflamed paw at doses of 0.02-0.2 mg/kg and did not affect the hyperthermia at doses of 0.4 and 0.6 mg/kg. The combined action of clemastine and EHF EMR exposure caused a dose-dependent abolishment of the anti-inflammatory effect of EHF EMR. The results obtained suggest that both arachidonic acid metabolites and histamine are involved in the realization of anti-inflammatory effects of low-intensity

Lack of direct DNA damage in human blood leukocytes and lymphocytes after in vitro exposure to high power microwave pulses.

Currently, the potential genotoxicity of high power microwave pulses (HPMP) is not clear. Using the alkaline single cell gel electrophoresis assay, also known as the alkaline comet assay, we studied the effects of HPMP (8.8 GHz, 180 ns pulse width, peak power 65 kW, pulse repetition frequency 50 Hz) on DNA of human whole-blood leukocytes and isolated lymphocytes. The cell suspensions were exposed to HPMP for 40 min in a rectangular waveguide. The average SAR calculated from the temperature kinetics was about 1.6 kW/kg (peak SAR was about 300 MW/kg). The steady-state temperature rise in the 50 microl samples exposed to HPMP was 3.5 +/- 0.1 degrees C. In independent experiments, we did not find any statistically significant DNA damage manifested immediately after in vitro HPMP exposure of human blood leukocytes or lymphocytes or after HPMP exposure of leukocytes subsequently incubated at 37 degrees C for 30 min. Our results indicate that HPMP under the given exposure conditions did not induce DNA strand breaks, alkali-labile sites, and incomplete excision repair sites, which could be detected by the alkaline comet assay.

[Study of endothelium-dependent blood oscillations in the human skin microcirculatory bed].

Cutaneous microcirculation parameters were studied with laser Doppler flowmetry in healthy volunteers. To investigate endothelial-dependent peripheral blood flow oscillations the iontophoresis of 1% acetylcholine solution was carried out. To estimate the contribution of rhythmical components in blood flow signal the continuous wavelet-transform spectral analysis was used. To reveal correlation between microcirculation parameters under study the correlation analysis was used. The microcirculation index was shown to be the factor producing cross-correlation dependences. The only positive significant correlation between the blood flow oscillation amplitude in the range of endothelial activity normalized to mean microcirculation index at rest and maximal microcirculation index during the iontophoresis of acetylcholine was revealed.